Motor asymmetry and estimation of body-scaled aperture width in Parkinson's disease

Neuropsychologia 49 (2011) 3002–3010

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Motor asymmetry and estimation of body-scaled aperture width in Parkinson’s disease J.G. Smith a,1 , J.P. Harris a,∗ , S. Khan b , E.A. Atkinson a , M.S. Fowler a , D. Ewins c , S. D’Souza c , R.P. Gregory b , R.J. Kean a a

School of Psychology and Clinical Language Sciences, University of Reading, Whiteknights, Reading RG6 6AL, UK Department of Neurology, Royal Berkshire NHS Foundation Trust, London Road, Reading RG1 5AN, UK c Centre for Biomedical Engineering, Duke of Kent Building, University of Surrey, Guildford, Surrey GU2 7TE, UK b

a r t i c l e

i n f o

Article history: Received 16 November 2010 Received in revised form 15 June 2011 Accepted 27 June 2011 Available online 2 July 2011 Keywords: Motor asymmetry Parkinson’s disease Visuospatial Body representation External space

a b s t r a c t The present study examined how asymmetrical motor symptomatology helps predict the pattern of perceptual judgements of body-scaled aperture width in lateralised Parkinson’s disease (PD). Eleven patients with PD predominantly affecting the left side of their body (LPD), 16 patients with PD predominantly affecting their right side (RPD), and 16 healthy controls made forced-choice judgements about whether or not they would fit without turning their shoulders through a life-sized schematic doorway shown on a large screen. Whereas control and LPD groups made accurate estimations of body-scaled aperture width, RPD patients significantly underestimated aperture width relative to their body, perceiving doorways on average that were 12% narrower than their bodies as wide enough to allow them to pass through without rotation. Across all patients, estimates of body-scaled aperture width correlated with ratio of right-to-left symptom severity. These perceptual errors may indicate a mismatch between the neural representation of external space and that of body size in PD. © 2011 Elsevier Ltd. All rights reserved.

1. Introduction Difficulties with spatial navigation are among the most distressing problems experienced by people with Parkinson’s disease (PD). While these often reflect motor symptoms, such as rigidity, bradykinesia, and postural instability, many patients report that going through doorways, narrow corridors, and other confined spaces causes freezing or festinating gait, and/or leads to an increased likelihood of collisions, indicating a likely perceptual and/or attentional component to navigational problems (Lee & Harris, 1999; Rahman, Griffin, Quinn, & Jahanshahi, 2008; Schaafsma et al., 2003). One explanation for mobility problems in confined spaces in PD is that attention is diverted from organising voluntary movements by objects in peripheral vision, such as the surrounds of doorways (McDowell & Harris, 1997). Consistent with this hypothesis, patients are more susceptible to visual distracters in peripheral vision (Deijen, Stoffers, Berendse, Wolters, & Theeuwes, 2006; Machado, Devine, & Wyatt, 2009). A general impairment in visual

∗ Corresponding author. Tel.: +44 118 3787534; fax: +44 118 3786815. E-mail address: [email protected] (J.P. Harris). 1 Present address: Division of Population Health Sciences and Education, St. George’s University of London, Cranmer Terrace, London SW17 ORE, UK. 0028-3932/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2011.06.025

attention is shown by the failure in PD to benefit from valid spatial cues, or to follow instructions not to look directly at stimuli presented in the periphery (Sampaio et al., 2011). A second type of explanation for mobility problems is that changes to spatial vision and/or proprioception affects navigation in cluttered environments in PD (Lee, Harris, Atkinson, & Fowler, 2001a; Rahman et al., 2008). Disturbances to visuospatial processing are common in PD (Davidsdottir, Cronin-Golomb, & Lee, 2005; Lee & Harris, 1999; Lee, Harris, Atkinson, & Fowler, 2001b) especially in patients with symptoms predominantly on their left (LPD) rather than right (RPD) side, for example, in line bisection, optic flow perception, and tasks involving saccades to a target (Davidsdottir, Wagenaar, Young, & Cronin-Golomb, 2008; Starkstein, Leiguarda, Gershanik, & Berthier, 1987; Ventre, Zee, Papageorgiou, & Reich, 1992). In these studies, the LPD, but not the RPD, groups often show signs of directional neglect, suggesting a lateralised visuospatial or attentional deficit. Changes to proprioception in PD are also well known, although it is not clear how this is affected in asymmetric disease. In one study, Mongeon, Blanchet, and Messier (2009) reported that medicated RPD patients were less accurate when reaching to proprioceptively defined targets. Another recent study found constricted subjective self-referential conceptualization of space but only for LPD patients (Skidmore et al., 2009). Taken together then, such studies of perception in PD suggest that disrupted proprioceptive and visuospatial processing, most obvious in perceptual asymmetries in lateralised disease,

J.G. Smith et al. / Neuropsychologia 49 (2011) 3002–3010

may have roles in patients’ difficulties in interacting with the local environment. Asymmetries of motor impairment in PD, which appear to persist across the range of disease severity (Hoehn & Yahr, 1967), reflect asymmetric depletion of dopamine in the substantia nigra, as shown by single-photon emission tomography and positron emission tomography (Booij et al., 1997; Kaasinen et al., 2001). Further, marked asymmetry of dopaminergic activity in the putamen and caudate persists even in severe bilateral motor disability (Booij et al., 1997). This results in asymmetrical dysregulation of the striatum, leading to further asymmetrical dysfunction of multiple circuits involving the basal ganglia and cortical regions, including temporo-parietal regions important for visuospatial cognition (Clower, Dum, & Strick, 2005; Middleton & Strick, 2000). These asymmetries in dopaminergic regulation of the cortex are likely to be the neural substrate of the observed links between motor asymmetries and the greater impairment of spatial processing in LPD, since, for example, the right parietal lobe is known to be critical for processing spatial information (Fink et al., 2000). There are suggestions that the perceptual differences between LPD and RPD may be important in navigating through apertures, such as doorways, in natural cluttered environments. Thus, although both LPD and RPD frequently report bumping into the sides of doorways (Davidsdottir et al., 2005; Lee & Harris, 1999), RPD report bumping equally into the left and right sides of doorways, whereas LPD primarily report bumping into the left side of doorways (Davidsdottir et al., 2005). This suggests that collisions may have a different origin in the two groups, an idea tested by Lee et al. (2001a) who asked participants to judge whether they could fit through life-sized schematic doorways without rotating the body. Their LPD group required a doorway of about 1.5 times body width, and the RPD group one of 0.9 times (compared with the 1.1 times of the controls) before judging that they would fit through. The authors speculated that these differences in body-scaled aperture judgements arose because, in LPD, the (right hemisphere-based) visuospatial representation of external space is shrunk, whereas, in RPD, the (left hemisphere-based) representation of the body may be shrunk. This interpretation is broadly consistent with findings that LPD patients are impaired in mental manipulations of external objects, while RPD show deficits in mental manipulations of their own body relative to space (Amick, Schendan, Ganis, & Cronin-Golomb, 2006), and, more generally, with the hypothesis that whereas regions in the right hemisphere are necessary for object-centred transformations, there is a left-hemisphere advantage for viewer-centred transformations (Cronin-Golomb, 2010). There is also evidence that the magno-cellular visual pathway, which provides input to the right parietal lobe, is impaired in PD, in addition to any direct effects of the illness on parietal function (Silva et al., 2005). An important but largely neglected question is that of exactly how asymmetries in motor impairment are related to changes in spatial perception, and so the nature of the underlying perceptual processes. Like most previous studies of visuospatial function in asymmetric disease, investigations of body-centred representations of visual space in PD have relied on patient classifications based on side of symptom onset or side of the body on which symptoms were worse at the time of testing (Lee et al., 2001b; Skidmore et al., 2009). Such a binary classification has the merit of simplicity, but patients typically exhibit bilateral motor impairments, and placing patients into left- or right-sided groups can result in a distinction that is not necessarily clinically applicable, and potentially discards up to half of their symptoms (Cooper et al., 2008). More specifically, such an approach fails to take into account the precise level of motor impairment on the most affected side (and by implication the extent of dopaminergic dysfunction in the con-

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tralateral hemisphere) as well as the degree of asymmetry of motor impairment (the extent of dopaminergic dysfunction in one hemisphere relative to that in the other), factors which may be important in visuospatial processing in PD. For example, two recent studies have reported that the degree of right-sided symptoms in patients was specifically related to visuospatial performance (Cooper et al., 2008; Smith et al., 2010). Further, Foster, Black, Antenor-Dorsey, Perlmutter, and Hershey (2008) recently found that visuospatial memory impairment was related to the degree of asymmetry of motor signs in early PD, with worse performance in those with worse left-sided symptoms. The importance of the method of classifying patients was also apparent in the study by Cooper and colleagues, since when subsets of patients with predominantly right- and predominantly left-sided symptoms were compared, there were no significant differences in visuospatial performance between the groups. Together, then, these studies emphasise the need to consider the precise level of hemispheric impairment in lateralised PD in examinations of visuospatial processing (as well as the nature of the visuospatial task). The purpose of the present study was to examine judgements of body-scaled aperture width in PD and healthy controls. The perceptual task used closely followed that of Lee and colleagues (2001a), in which seated participants judged whether or not the widest part of their body (taken to be the shoulders) would fit through a series of schematic doorways without turning. A battery of standard neuropsychological tests was also administered, including some with an attentional component. The study went beyond that of Lee et al. in using a different way of classifying the patients, and in varying the contrast and luminance of the doorway surrounds, and was designed to test three hypotheses: (1) The extent and direction of misjudgement of body-scaled aperture width would correlate with asymmetry of motor symptoms. (2) In patients, but not in controls, the misjudgements would be related to the perceptual salience of the aperture surrounds, and so to their ability to capture attention. (3) Attentional dysfunction, if indicated by the aperture judgement task, would be reflected in the other neuropsychological tests. 2. Method 2.1. Participants Twenty-seven patients with idiopathic PD and 16 age-matched healthy controls participated. Participants were screened for dementia using the Mini-Mental State Examination (MMSE cut-off = 24, Folstein, Folstein, & McHugh, 1975) and for depression using the Beck Depression Inventory-II (BDI-II cut-off = 17, Beck, Steer, & Brown, 1996).2 None had a history of head injury within the preceding 10 years, or of alcohol abuse, stroke, or epilepsy. The diagnosis of idiopathic PD was confirmed by a neurologist, who also allocated patients to a Hoehn and Yahr (1967) stage, and all patients met United Kingdom Parkinson’s Disease Brain Bank Criteria for diagnosis of PD (Gibb & Lees, 1988). Ethical approval for the study was given by the Berkshire NHS Research Ethics Committee and by the University of Reading Research Ethics Committee. All participants gave their informed consent after a verbal and a written description of what their participation would involve. 2.1.1. Clinical assessment All patients completed the 16-item Gait and Falls Questionnaire (GFQ; Giladi et al., 2000), which included six items specifically constructed to assess freezing of gait (FOG). The Unified Parkinson’s Disease Rating Scale Motor subscale was also used as a measure of current motor severity in PD patients and to classify patients into left- and right-sided PD groups (UPDRSm; Fahn, Elton, & Members of the UPDRS Development Committee, 1987). The UPDRS was administered by the neurologist blind to experimental results once after a minimum 10-h withdrawal from dopaminergic medication (mean withdrawal period was 13 h 29 min, standard deviation [SD] = 2 h 51 min) and then again 40–75 min after the usual PD medication (when the

2

Scheduling limitations prevented one patient from completing the BDI-II.

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Table 1 Demographic and clinical data for predominantly left-sided Parkinson’s disease (LPD), predominantly right-sided Parkinson’s disease (RPD) and control participants. Variable/Measure

LPD Patients (n = 11)

RPD Patients (n = 16)

Controls (n = 16)

Sex (M/F)

n 7/4

n 13/3

n 10/6

Age (years) Education (years) MMSE BDI-IIa Disease duration (years) UPDRSm ‘OFF’b Right-sided symptoms ‘OFF’ Left-sided symptoms ‘OFF’ Motor asymmetry score ‘OFF’ UPDRSm ‘ON’ Right-sided symptoms ‘ON’ Left-sided symptoms ‘ON’ Motor asymmetry score ‘ON’ GFQ total Freezing of gait component

Mean (SD) 66.14 (7.9) 12.22 (2.5) 29.00 (1.1) 8.18 (4.8) 6.59 (4.5) 28.70 (4.8) 6.30 (1.8) 13.60 (2.6) 0.37 (0.1) 18.09 (3.2) 4.91 (1.7) 7.09 (1.1) 0.20 (0.1) 9.82 (8.7) 6.36 (4.8)

Mean (SD) 70.39 (8.1) 13.13 (2.2) 28.13 (1.4) 8.63 (4.3) 6.13 (4.4) 25.63 (9.2) 12.06 (4.2) 5.69 (4.3) −0.45 (0.3) 18.44 (6.3) 7.94 (2.5) 3.88 (3.1) −0.44 (0.3) 19.31 (14.0) 9.56 (6.7)

Mean (SD) 67.07 (5.9) 13.50 (3.1) 29.06 (0.9) 5.13 (3.7)

2 -Value

p-Value

1.60

0.450

F-Value 1.34 0.76 3.07 3.11 0.07 0.95 16.74 28.03 74.37 0.03 12.27 10.49 39.38 3.98 1.85

p-Value 0.273 0.474 0.058 0.055 0.791 0.340 <0.001 <0.001 <0.001 0.868 0.002 0.003 <0.001 0.057 0.186

Note. MMSE = Mini Mental Status Examination; BDI-II = Beck Depression Inventory II; UPDRSm ‘OFF’ = Score on motor subscale of Unified Parkinson’s Disease Rating Scale after overnight withdrawal of medication. UPDRSm ‘ON’ = Score on motor subscale of Unified Parkinson’s Disease Rating Scale post administration of medication; Motor asymmetry score = (UPDRSm Right − UPDRSm Left)/(UPDRSm Right + UPDRSm Left); GFQ = Gait and Falls Questionnaire. P values shown in bold indicate significance at the 5% level or better. a One LPD patient did not complete the BDI-II. b One LPD patient was administered the motor subscale of the UPDRS post medication only (in the ‘ON’ state).

patient was in an ‘ON’ state). The first motor assessment was conducted to reduce variability in motor function produced by medication (since some patients might be under- or over-medicated), while the second was administered when patients were in the same state (the ‘ON’ state) as when all experimental tasks were performed. Of note, one patient was examined in an ‘ON’ state only while another took medication 4 h before the initial assessment. Nevertheless, this patient was in a selfreported ‘OFF’ state for the assessment, and this was confirmed by the neurologist. For each assessment, right- and left-sided motor composite scores were created by summing the individual UPDRS subscale items of tremor (items 20 and 21), rigidity (item 22) and bradykinesia (items, 23, 24, 25, and 26). Degree of asymmetry of dysfunction was determined by calculating a motor asymmetry score using the left and right motor composite scores obtained from patients: (UPDRSm Right − UPDRSm Left)/(UPDRSm Right + UPDRSm Left). This formula gives a result of zero when left and right motor scores are equal, a negative number when left symptoms are worse, and a positive number when right symptoms are worse. Based on the scores after withdrawal from dopaminergic medication, patients were divided into two groups for comparison with the data of Lee et al. (2001a), those with motor symptoms predominantly on the left (LPD, n = 11), and those with symptoms predominantly on the right (RPD, n = 16). LPD asymmetry scores ranged from −0.25 to −0.55 and RPD scores from 0.04 to 1.00. The demographic and clinical characteristics of the participant subgroups are shown in Table 1. There was a higher proportion of males in the RPD group compared with both the LPD and control groups, although differences between the PD subgroups (p = 0.39) and between RPD patients and controls (p = 0.43, Fisher’s exact tests) were not significant. Groups were well matched on age and education (from two-tailed t-tests, comparing each pair of experimental groups, no differences were significant). All groups’ mean MMSE scores were consistent with or greater than age-normative data (Crum, Anthony, Bassett, & Folstein, 1993), and although BDI-II scores were elevated in each of the patient subgroups relative to controls (for both comparisons, p < 0.021), the scores of the PD subgroups were comparable with each other (t(24) = 0.24, p = 0.79) and within the normal range. The PD subgroups were also matched on illness-related variables, including disease severity and medication regimes. As assessed by the Hoehn and Yahr (1967) degree of clinical disability scale, 5 patients (2 LPD, 3 RPD) were in Stage I, 15 patients (7 LPD, 8 RPD) were in Stage II, 6 patients (2 LPD, 4 RPD) were in Stage III, and one (RPD) patient was in Stage IV. Severity of stages did not significantly differ between PD groups, U(25) = 78, p = 0.584. One-way ANOVAs also revealed no significant difference between the subgroups in disease duration and total UPDRSm, both in ‘ON’ and ‘OFF’ states. Unsurprisingly, left-sided UPDRSm scores (in both ‘ON’ and ‘OFF’ state) were higher in LPD than in RPD, while motor symptoms on the right side of the body were more severe in RPD than LPD. Motor asymmetry scores were also significantly different between the RPD and LPD groups (p < 0.001; see Table 1), reflecting RPD participants’ scores that were positive and LPD participants’ scores that were negative. The motor symptoms of the RPD group were more asymmetric than were those of the LPD group as revealed by a comparison of the absolute values of group motor asymmetry scores, although this difference was only significant in the case of ‘ON’ scores, F(1,26) = 5.54, p = 0.027. At the time of experimental testing all 27 patients with PD were receiving anti-Parkinsonian medication. Specifically, 3 of the (RPD) patients were receiving dopamine precursor levodopa (Stalevo,

Sinemet and/or Madopar) exclusively, while 4 patients (2 LPD, 2 RPD) were taking dopamine agonists (Pramipexole, Ropinirole, Rotigotine) exclusively. Fifteen of the patients (7 LPD, 8 RPD) were taking both levodopa and agonist medication, of which 2 (LPD patients) were also receiving Amantidine, 3 patients (1 LPD, 2 RPD) receiving a selective monoamine-oxidase-B inhibitor (MAO-B) inhibitor (Selegeline or Rasagiline), and one (LPD) receiving both Amantidine and a MAO-B inhibitor. One RPD patient undergoing levodopa treatment (but not agonist treatment) was also being administered both a MAO-B inhibitor (Selegeline) and a catechol-O-methyl tranferase (COMT) inhibitor (Entacapone). Three patients who were taking dopamine agonists (but not levodopa) were receiving other medications as well; one (LPD) taking Amantidine, one (LPD) taking anticholinergic medication (Trihexphenidyl); and another (RPD) receiving both a MAO-B inhibitor (Selegeline) and anticholinergic medication (Trihexphenidyl). Finally, one RPD patient was receiving a MAO-B inhibitor (Rasagiline) exclusively. Fisher’s exact tests indicated that the PD subgroups were not significantly different in the number of participants treated with levodopa medication (LPD: 7/11, RPD: 12/16, p = 0.675), but there was a trend for LPD patients to be more likely than RPD to be receiving dopamine agonists (LPD: 11/11, RPD: 11/16, p = 0.060). Of note, one LPD patient was also receiving SSRI antidepressant medication (Fluoxetine). Interestingly, despite the comparability of the PD subgroups in terms of motor dysfunction as gauged by the UPDRSm, responses to the GFQ suggested that, except for freezing, the RPD group suffered from difficulties with gait to a greater degree than their left-sided counterparts (see Table 1). Visual contrast sensitivity can be impaired in PD (Bodis-Wollner et al., 1967; Sampaio et al., 2011), and around 50% of patients report experiencing double vision (Lee & Harris, 1999). Aspects of basic visual function were therefore assessed as follows in all but three of the patients who experienced scheduling difficulties (10/11 LPD; 14/16 RPD). Visual acuity was measured in each eye with the Times Roman Reading Charts of the MaclureTest (Clement Clarke International Ltd.), on which the ability to read a type size of N6 at the normal reading distance corresponds approximately to a Snellen Acuity of 6/6. Taking acuity in the worst eye when the eyes were not equal, the mean acuity of the LPD group was N5.60 (range N5–N8), while all patients in RPD group read at N5. Two tests of stereopsis were also run. On the Randot test of stereopsis, the scores were: LPD, mean (M) = 126.56 (SD = 185.13, range = 20–600); RPD, M = 72.14 (SD = 51.91, range = 20–200). On the TNO test of stereopsis, the scores were: LPD, M = 465.00 (SD = 800.66, range = 30–1980); RPD, M = 277.79 (SD = 272.44, range = 60–860). In a healthy elderly group, mean scores on the Randot test of 45 and on the TNO test of 275 were found (Fowler, 1996). In a group of normal participants, whose ages ranged from 4 to 74 years, a mean Randot score of 44 and a mean TNO score of 194 were found (Mazow, Prager, & Cathey, 1983). Thus, although the trend in both patient groups was for worse performance than normal on the Randot test, the RPD group had a similar threshold to Fowler’s healthy elderly group on the TNO. The LPD group had higher thresholds than normal on the TNO, but clearly retained some stereoscopic vision. On clinical examination, all patients bar one RPD patient (bilateral restriction of elevation) showed the full range of ocular movements. One LPD and one RPD patient showed a slight saccadic hypometria (left > right). Pursuit eye-movements were sometimes jerky in three LPD and ten RPD patients. All patients could converge on a near point of 20 cm or less except for two LPD patients (25 cm, 30 cm) and two RPD patients (30 cm, 40 cm). Thus, we conclude that the patients were not suffering from gross disorders

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Table 2 Neuropsychological test results for predominantly left-sided Parkinson’s disease (LPD), predominantly right-sided Parkinson’s disease (RPD) and control participants. Measure

LPD patients (n = 11) Mean (SD)

RPD patients (n = 16) Mean (SD)

Controls (n = 16) Mean (SD)

LPD vs. RPD t

LPD vs. Ctrl t

RPD vs. Ctrl t

NART COWAT ANT CERAD total trials 1–3 (0–30) CERAD delayed recall (0–10) Stroop A Stroop B Stroop A–Stroop B TMT A TMT B TMT B–TMT A

115.78 (7.7) 42.73 (12.3) 21.64 (4.0) 17.55 (4.6) 4.45 (1.6) 84.09 (14.7) 40.18 (10.9) 43.91 (9.1) 47.81 (15.9) 160.86 (100.5) 113.05 (94.2)

117.26 (8.7) 40.38 (12.9) 22.13 (6.0) 16.62 (3.7) 4.75 (2.3) 80.44 (13.9) 41.94 (10.6) 38.50 (13.5) 44.82 (16.1) 115.59 (39.8) 70.77 (32.4)

117.21 (8.5) 43.38 (11.8) 27.88 (6.8) 21.75 (3.0) 6.56 (1.6) 86.88 (14.6) 48.56 (15.5) 38.31 (11.3) 35.80 (17.3) 111.48 (99.4) 75.69 (87.3)

−0.46 0.48 −0.24 0.57 −0.37 0.66 −0.42 1.16 0.48 1.42 1.43

−0.45 −0.14 −2.75* −2.90** −3.35** −0.49 −1.54 1.36 1.83 1.26 1.06

0.02 −0.69 −2.55* −4.29*** −2.60* −1.28 −1.41 0.04 1.53 0.15 −0.21

Note. NART = National Adult Reading Test (expressed as a Wechsler Adult Intelligence Scale – Revised Full Scale equivalent); COWAT = Controlled Oral Word Association Test; ANT = Animal Naming Test; CERAD = wordlist memory test from the Consortium to Establish a Registry for Alzheimer’s Disease battery; TMT = Trail Making Test. P values shown in bold indicate significance at the 5% level or better. * p < 0.05. ** p < 0.01. *** p < 0.001.

of acuity or binocularity which would interfere with their perception of the aperture and surrounds at the experimental viewing distance.

2.1.2. Neuropsychological assessment All participants were administered a small battery of neuropsychological tests, which included the National Adult Reading Test (NART; Nelson & Willeson, 1991) as well as measures of verbal fluency, specifically, the Controlled Oral Word Association Test (COWAT; Benton & Hamsher, 1976) and the Animal Naming subtest from the Boston Diagnostic Aphasia Examination (ANT; Goodglass & Kaplan, 1972). Participants also performed the Stroop task and the Trail Making Test, while verbal memory was assessed using the wordlist memory test from the CERAD battery (Consortium to Establish a Registry for Alzheimer’s Disease; Rosen, Mohs, & Davis, 1984). A summary of the neuropsychological test results is displayed in Table 2. With the exception of the NART, controls tended to perform better than both PD groups on all measures. However, two-tailed t-tests comparing control scores with each PD subgroup separately revealed significant group differences only for measures related to memory (total immediate recall and delayed recall) on the CERAD, associated with hippocampal atrophy in PD (Jokinen et al., 2009), and on the ANT, a measure of semantic verbal fluency, associated with frontal lobe activity (see e.g., Costafreda et al., 2006). Notably, t-tests comparing the PD subgroups showed comparable performance on all measures, suggesting the neuropsychological profiles of the patient groups were similar. Although the cost of incongruent colour-word condition on the Stroop and task switching on the Trail Making Test was numerically greater for LPD patients, suggesting mildly impaired executive abilities in the LPD subgroup relative to their RPD counterparts, the differences failed to approach significance in both cases (p > 0.05).

2.3. Procedure Each participant viewed the display at a distance of approximately 1.14 m. Participants were positioned so that they were aligned with the mid-point of the screen and of the doorways. They were asked to imagine that they were sitting on a narrow trolley which could be moved along a railway track running through the centre of the doorway. The aim of this instruction was to allow participants to ignore any problems with their gait. Their task was to judge whether their bodies would fit through the doorway without them rotating their shoulders. Using the index finger of each hand, they pressed one pushbutton to signal ‘yes’ and the other to signal ‘no’. The lateral positioning of the ‘yes’ and ‘no’ buttons (and hence the hand associated with ‘yes’ and ‘no’ responses) was counterbalanced across participants within each experimental group. A double interleaved staircase procedure was used to find the door width which participants reported that they could pass through without shoulder rotation on 50% of the trials. One staircase began with a doorway width of 36 cm, the other with a width of 72 cm, and they were randomly chosen on each trial. On each presentation, the doorway appeared and remained on the screen until a response was made. If a response was ‘yes’, width was reduced on the next presentation, and if ‘no’, width was increased. Width was stored if the response changed from ‘yes’ to ‘no’ (or vice versa) from the previous presentation on that staircase to the current presentation (a reversal). There was then an interval of 1.5 s before the next presentation began. Initial step size on each staircase was 0.12 log units, reducing to 0.03 log units after two reversals and to 0.015 log units after four reversals. Each staircase terminated after 10 reversals, and the mean doorway width at reversal was calculated from the last 6 reversals on each staircase. After these exper-

2.2. Stimuli and apparatus Stimuli for the aperture judgement task were generated by an IBM-compatible computer at XVGA (1600 × 1200 pixel) resolution and back-projected by a Christie DS+25 projector on a large translucent screen (2 m wide × 2.4 m high). Responses were recorded via a two-pushbutton response panel interfaced with the PC. One button was red, and had a label ‘NO’ next to it, and the other was green, and had the label ‘YES’ next to it. The response panel was positioned so that the buttons were side by side, and was aligned with the centre of the screen. The stimulus was a schematic doorway, like the goal posts in soccer, consisting of two uprights and a cross bar or lintel. Participants were seated in a chair with arm rests, positioned so that its midline was aligned with the midline of the doorway and of the screen (see Fig. 1). The thickness of the uprights was 4.5 deg and the lintel 3.8 deg, while the separation of the uprights could be varied under program control with a resolution of 3.4 (1 pixel). In one condition, the surround to the doorway was plain beige. In the other three it was filled with stripes, either high contrast (black/white) horizontal, low contrast (dark beige/light beige) vertical, or high contrast vertical. The black and dark beige stripes were 35 wide and the interstripe spacing (white and light beige) was 43 . The order of the surround conditions was counterbalanced across participants within each experimental group. Measured with a Minolta CS-100 Chroma Meter, the luminances of the various regions of the display were as follows: uprights/lintel, 245 cd m−2 ; aperture, 37 cd m−2 ; plain beige surround, 202 cd m−2 ; black stripes, 20 cd m−2 ; white stripes, 232 cd m−2 ; light beige stripes, 236 cd m−2 ; dark beige, 202 cd m−2 . Measured with the Chroma Meter, the CIE x and y chromaticity coordinates of the surround hues were: white, 0.326 and 0.344; and beige, 0.332 and 0.350. The aim of varying the contrast of the stripes was to vary their visual salience, and so their ability to grab attention.

Fig. 1. Schematic view of the aperture judgement task from behind the participant, who sat at a bench facing a large screen, on to which images of doorways were back projected. The doorway width was varied on successive presentations, and the participant judged whether they would fit through the doorway without turning their shoulders, signalling their judgement by pressing one of two push-buttons. In different conditions, the properties of the door surrounds were high contrast vertical stripes (shown above), high contrast horizontal stripes, low contrast (dark beige/light beige) vertical stripes or plain beige.

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Fig. 2. Mean aperture-to-shoulder width (A/S) ratios on the aperture judgement task for each of the patterned surrounds in predominantly left-sided Parkinson’s patients (LPD), predominantly right-sided Parkinson’s patients (RPD), and control participants. Error bars represent the standard errors of the means.

iments, each participant’s body width was measured at the shoulders with a large caliper, and the ratio between the widest part of the body (just below the shoulders) and perceived adequate doorway width was calculated (the aperture/shoulder, or A/S, ratio).

3. Results 3.1. Relationship between motor symptoms and aperture judgements The mean A/S ratios for each surround are depicted in Fig. 2. It is clear from the figure that the doorways perceived as just adequate by controls and LPD patients were wider than those for the RPD patients who, on average, tended to perceive a doorway which was 12% narrower than their bodies as sufficiently wide to allow them to pass through without rotation. Collapsed across all surrounds, total mean A/S ratio for RPD patients was 0.88 (SD = 0.14) compared to 1.06 (SD = 0.18) for controls and 1.03 (SD = 0.16) for LPD patients. Data were analysed with a mixed-model ANOVA in which the Between-Subject factor was Groups (3) and the Within-Subject factor was Surround Pattern (4). This showed a significant main effect of Surround Pattern, F(3,120) = 3.59, p = 0.013, MSE = 0.004, reflecting the general shift towards lower A/S ratios in high contrast striped surrounds, most notably those with vertically oriented stripes. Most importantly, there was a significant effect of group, F(2,40) = 5.14, p = 0.010, MSE = 0.103. However, the interaction between Group and Surround Pattern was not significant, F(6,120) = 0.77, p = 0.60, suggesting that A/S ratios were similarly reduced by high contrast stripes in all groups. The mean total A/S ratios for the two patient groups were compared with that of the control group, using Dunnett tests (Winer, 1971). This revealed significant differences between RPD and LPD patient groups (p = 0.042) and RPD patients and controls (p = 0.009), but not between LPD patients and controls (p = 0.91). Notably, within each patient subgroup, 10 out of the 16 (62.5%) RPD patients produced an overall A/S ratio less than 0.9 (i.e., judged that they would fit through apertures that were more than 10% less than their shoulder width) whereas only 1 of the 11 (9.1%) LPD patients had an A/S ratio less than 0.9 (2 (26) = 7.70, p = 0.006). Particularly because of the differences in group sample sizes, we checked for homogeneity of variances of the A/S ratios for the four surround types separately, as well as for the mean A/S ratios. Since the largest Levene statistic was

0.77 (p = 0.47), we conclude that the assumption of homogeneity of variances was not violated in our data. Visuospatial impairments have been related to symptom severity on one side of the body irrespective of symptom severity on the other side (Cooper et al., 2008) and with the degree of asymmetry in degeneration of the basal ganglia volume (Foster et al., 2008). Therefore, we investigated the relationship between severity of left- and right-sided symptoms and asymmetry scores with A/S ratio on the doorway judgement task. Correlational analyses (Pearson) involving all PD patients revealed that the overall A/S ratio (collapsed over surrounding patterns) was not significantly (positively) related to the severity of left-sided symptoms (scores on the motor subscale of the UPDRS) in either the ‘ON’ state r(26) = 0.18, p = 0.371, or the ‘OFF’ state, r(25) = 0.36, p = 0.068, or significantly (negatively) related to the severity of right-sided symptoms in either the ‘ON’ state r(26) = −0.21, p = 0.292, or the ‘OFF’ state, r(25) = −0.24, p = 0.235. However, A/S total ratio was significantly associated with the ratio of right-to-left motor symptoms: in PD patients after 12-h dopaminergic medication withdrawal (in an ‘OFF’ state), r(25) = −0.39, p = 0.047. 3.2. Effects of surrounds The fact that A/S ratios were, generally speaking, highest for the beige and low contrast striped surrounds and lowest for the high contrast striped conditions, suggests that the orientation of stripes in surrounds was less important in the perception of width of schematic doorways than their contrast (or mean luminance, since this was lower for the high contrast surrounds). A mixedmodel Groups (3) × Surround Pattern (2) ANOVA in which the beige and low contrast stripes were collapsed into one single factor and the high contrast vertical and horizontal striped surrounds were collapsed into another single factor, appeared to confirm this hypothesis, as there was a highly significant effect of ‘Surround Pattern’, F(1,40) = 7.37, p = 0.010, MSE = 0.002, although again no significant interaction with Group, F(2,40) = 1.32, p = 0.28. 3.3. Relationships between aperture judgements and neuropsychological measures Despite the absence of a significant interaction between participant group and surround properties, it is possible that the degree of change (decrease) in perceived doorway width induced by the high contrast surrounds was related to clinical factors or neuropsychological performance in PD, especially given the very low A/S ratios observed in the RPD group. Exploratory analyses (not corrected for family-wise error) using Pearson correlations on all PD patients showed that the change in A/S ratio (calculated by subtracting the collapsed A/S ratio from the high contrast vertical and horizontal striped surrounds from the A/S ratio in the plain beige surround3 ) was significantly associated only with patients’ age (r(26) = 0.47, p = 0.020), and the Stroop A–B score (r(26) = −0.47, p = 0.014), and not to clinical measures of Parkinsonian features, such as UPDRSm scores, motor asymmetry scores, duration of illness, and GFQ and FOG scores (for all associations, p > 0.05). Subsequent exploratory analyses revealed that total A/S ratios of PD patients were not significantly predicted (Pearson correlations, p > 0.05) by performance on any administered neuropsychological measure (see Table 1), suggesting that body-scaled judgements of aperture width in PD were not related to cognitive functioning (e.g., mnemonic and executive abilities). Nor did performance appear to be closely linked to gender (or the slightly different distribution

3 Note, the intra-correlation of the change scores between high contrast horizontal stripes and the beige surround and high contrast vertical stripes and the beige surround was very high in PD patients, r(26) = 0.70, p < 0.001.

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of males and females within each subgroup). Although A/S ratios in females tended to be larger than in males (LPD, Male, M = 0.98 SD = 0.15; Female, M = 1.12, SD = 0.14; RPD, Male, M = 0.87, SD = 0.15; Female, M = 0.94, SD = 0.07), these differences were not significant on t-tests (p > 0.05) although small numbers could have precluded significant findings. Notably, significant difference between patient groups remained after controlling for the effect of gender (from the ANCOVA, with gender as a covariate, F(1,24) = 5.12, p = 0.033, MSE = 0.103). Similarly, A/S ratios were highly comparable between patients taking levodopa and patients not taking levodopa within each patient group and between patients receiving dopamine agonist medication versus not taking agonists in the RPD group (for all comparisons using t-tests, p > 0.05). Again, group differences between LPD and RPD in total A/S ratios remained after accounting for whether or not patients were receiving levodopa and agonist treatment (from the ANCOVA, with levodopa or not, and agonist or not, as covariates, F(1,23) = 4.52, p = 0.044, MSE = 0.109). Interestingly, despite the trend towards greater gait impairment (as measured by the GFQ) in the RPD group compared to the LPD group, and the pattern of abnormal judgements on the aperture width task in RPD patients, Pearson correlations between total A/S ratio and GFQ and FOG scores failed to reach statistical significance: for GFQ, r(10) = −0.23, p = 0.25; for FOG, r(10) = −0.13, p = 0.48. 4. Discussion 4.1. Aperture judgements and laterality Safely moving through apertures is a complex process that involves perceiving the relationship between the size of the opening and that of one’s own body. The present study examined the ability of people with lateralised PD and age-matched healthy controls to judge the aperture width at which they could just pass through without shoulder rotation. Averaged across conditions, the aperture-to-shoulder width (A/S) ratio for the control group was 1.05. In other words, they reported that they could just pass through an aperture which was 5% wider than their bodies. A/S ratios in LPD were also close to 1, indicating that their judgements of aperture affordance were accurate. However, RPD patients selected doorways that were on average more than 10% smaller than themselves. The importance of asymmetric motor dysfunction in PD was further confirmed in correlative analysis with all patients, showing a significant relationship between total A/S score and the ratio of right-to-left symptoms, suggesting that it is the relative impairment of the hemispheres which governs performance in PD on this task. The accuracy of controls’ judgements is in line with the findings of Lee et al. (2001a) and other comparable studies (LoprestiGoodman, Kallen, Richardson, Marsh, & Johnston, 2009; Warren & Whang, 1987), and consistent with the idea that healthy individuals know the fit between their own body and the environment (Gibson, 1979). The contrast between the two PD groups is also (broadly) consistent with previous research on perceptual abnormalities in PD (Davidsdottir et al., 2008; Lee et al., 2001a, 2001b; Schendan, Amick, & Cronin-Golomb, 2009), and further suggests there are differences in the spatial perception of predominantly left- and right-sided PD patients. In the present study, however, the leftsided group performed very similarly to healthy controls. Rather, a consistent underestimation of body-scaled aperture width was found for patients with predominantly right-sided symptoms. 4.2. Nature of possible impairments of spatial processing Decreased A/S ratios in RPD patients could reflect a change in the neural representation of external space or of the patient’s own

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body (or in both). Since it is the right hemisphere (particularly the parietal lobe) which is primarily associated with visuospatial processing (Fink et al., 2000), decreased A/S ratios in RPD probably reflect changes in the body-centred frame of reference, which much evidence suggests is mediated by the left hemisphere. For example, studies of autotopagnosia, a loss of spatial knowledge about one’s own body (Schwoebel, Coslett, & Buxbaum, 2001), and relatively selective deficits in the comprehension of body parts (Hillis & Caramazza, 1991; Suzuki, Yamadori, & Fujii, 1997; Warrington & McCarthy, 1987), have all involved patients with left hemisphere lesions. Furthermore, activity in somatosensory areas of left parietal cortex directly reflects the illusory sensation that the size and shape of the waist are changing (Ehrsson, Kito, Sadato, Passingham, & Naito, 2005). Proprioception is impaired in PD, as shown by perceptual-motor asymmetries and over-dependence on visual information in voluntary movements (Adamovich, Berkinblit, Hening, Sage, & Poizner, 2001; Davidsdottir et al., 2008; Wright, Gurfinkel, King, & Horak, 2007), and so body representations are likely to be abnormal, also. Most studies of proprioception in PD have not explicitly compared left- and right-sided patients (Adamovich et al., 2001; Mongeon et al., 2009) or have not reported any effect of motor symptom asymmetry (Wright et al., 2007), but there are reasons to suspect abnormal body representations in RPD. Thus, areas underlying visual attention and spatially guided behaviour, most notably posterior parietal cortex, are densely interconnected with basal ganglia structures, including the ventral putamen and head of the caudate nucleus (Clower et al., 2005; Middleton & Strick, 2000), both of which are depleted of dopamine even at the earliest stages of PD in an asymmetric fashion (Kish, Shannak, & Hornykiewicz, 1988). Interestingly, RPD patients are impaired in mental rotation of hands, implicating the left hemispheric in access to and manipulation of a representation of the body in space (Amick et al., 2006). Other studies have shown dissociations between LPD and RPD patients on tasks known to involve lateralised parietal lobe function, such as hierarchical pattern perception (CroninGolomb, 2010; Schendan et al., 2009) and egocentric midline shifting (Davidsdottir et al., 2008). The present findings are consistent with this evidence, though of course we did not make direct measurements of dopamine function in our patients. 4.3. Relationship to earlier work on aperture judgements in PD The results of the present study differ from those of Lee et al. (2001a) in an important way. Performance of the present LPD group was essentially normal, in contrast to the LPD group of Lee et al., who behaved as though underestimating aperture width. The present result was unexpected, given the evidence for the impact of left-sided disease on the representation of self-referential space (Lee et al., 2001a; Skidmore et al., 2009) as well as the perception of external space (Harris, Atkinson, Lee, Nithi, & Fowler, 2003; Lee et al., 2001b). The task requirements and methods of the two studies were alike in almost every way. Similarly, the (LPD) patient groups were generally comparable with respect to aspects of the disease such as Hoehn and Yahr stage of illness (predominantly Stages 1 and 2) and duration. Although Lee et al. did not use UPDRS in assessing motor symptoms, symptoms were assessed with similar scales. However, if damage to the left hemisphere in PD results in a constriction in the representation of (left) external space and damage to the right hemisphere damage leads to a shrinkage of perceived body size (as suggested by the correlation between A/S ratio and asymmetry of motor symptoms), then the direction and magnitude of spatial bias in PD may be more closely linked to the relationship between dopamine depletion in the two hemispheres, rather than the extent of damage in one hemisphere or the other. Thus, the absence of an abnormality of A/S ratios in LPD patients in

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the present study may reflect the smaller degree of asymmetry in the ‘ON’ state in this group than in the RPD group, whereas in the Lee et al. (2001a) study, the degree of asymmetry was much larger in the LPD than in the RPD group. In line with this hypothesis, in a study on almost identical patient groups, a strong left hemispace bias was found in a gender chimeric faces task in RPD but a negligible right hemispace bias in LPD (Smith et al., 2010). Most notably, left hemispace bias on the chimeric faces task was positively associated with the ratio of right-to-left motor symptom severity of all patients, irrespective of diagnosis, as was A/S ratio in the present study. 4.4. Effects of different surrounds As noted in Section 1, under some circumstances PD patients’ attention appears to be ‘grabbed’ by distracting visual stimuli which inhibit the programming of appropriate responses or voluntary movements. The aim of varying the contrast of the stripes in the aperture surround was to increase their visual salience, and so their ability to distract the patients, and so influence their aperture judgements. However, in the present study, PD patients were not affected more strongly than controls by the high contrast visual surrounds, but rather judgements of aperture width in all participant groups were similarly affected by an increase in surround contrast. Interestingly, the increase in perceived aperture width induced by the high contrast surrounds in PD was related to patients’ performance on the Stroop test, in that larger increases were associated with better performance (smaller A–B scores). Although Stroop performance is associated with activity in frontal cortex, there is also evidence for related parietal activity. However, this correlation appears to be negative. Thus, for example, in an fMRI study, Weiss et al. (2003) report a negative correlation between performance on the Stroop test and parietal activity. Consistent with this finding, Pujol et al. (2001) found, in a study of patients with multiple sclerosis, that those with parietal lesions showed superior performance (smaller A–B scores) on the Stroop test. On the assumption that, in our PD group, the Stroop test may in part reflect impairment in parietal structures mediating visual attention, the increase in perceived width is larger in those less able to ignore the more salient surrounds. Note, however, that Stroop performance did not distinguish between our PD subgroups or between patients and controls, which may be why the Group × Contrast interaction was insignificant. Thus, in this context, the small change in judged aperture width associated with a putative failure of attentional inhibitory processing seems to be a secondary effect, superimposed on a larger effect of changed spatial processing. In different circumstances, peripheral stimuli might become more important, as in the study of Sampaio et al. (2011), who showed that the usual right hemisphere dominance in visual attention is absent in PD (although, unfortunately for our purposes, they did not classify patients by laterality). During locomotion, visual transients produced by head and eye movements, and lower spatial frequencies in the surround patterns, might divert attention from the control of locomotion. Such pattern features would be likely to stimulate the magnocellular system, known to be especially important in peripheral vision (and to be impaired in PD – Silva et al., 2005).

of harm avoidance than do age-matched controls, this tends to be greater in LPD (Tomer & Aharon-Peretz, 2004). Thus, one would expect all patients to produce larger (not smaller) A/S ratios than controls and for the effect to be larger in LPD, a pattern very different from what was observed. Another possibility is that patients may have been made more impulsive by dopamine agonist treatment, since this can lead to impulse control disorders (ICDs) such as pathological gambling (Robert et al., 2009; Singh, Kandimala, Dewey, & O’Suilleabhain, 2007), or decreased weighting of negative consequences of decisions (Abler, Hahlbrock, Unrath, Grön, & Kassubek, 2009) and so some patients might have been more willing to accept smaller apertures as adequate. However, LPD patients, who were all taking agonists, performed normally, unlike the RPD patients, some of whom were not being treated with agonist medication. There is currently no evidence suggesting that susceptibility to ICDs is related to asymmetry of symptoms in PD (Gallagher, O’Sullivan, Evans, Lees, & Schrag, 2007; Singh et al., 2007). It could be argued that the association between the Stroop data and the change in aperture width with the high contrast surrounds reflects a failure of cognitive inhibition, and so an increase in reckless judgements. However, the direction of the effect is the opposite predicted by this hypothesis: larger decreases in A/S ratio (and so larger increases in the aperture width judged to be adequate) were associated with reduced, not greater, inhibition, as measured by the Stroop test. Recklessness implies that smaller, not larger, apertures would be judged to be adequate. Another possibility is that more random guesses in the RPD group might have increased the variability in the data, but it is not obvious how this could lead to systematic shifts in the mean selected aperture. Thus, there is no reason to suppose that changes of various kinds in response criteria underlay patients’ aperture judgements. 4.6. Variation of judged width with different surrounds It is not clear exactly why higher contrast surrounds led to decreased A/S ratios (the perception of apertures as being wider). In the Oppel-Kundt illusion, a filled space is perceived as being larger than an adjacent empty space of equivalent size, and this effect is heightened when the illusory figure consists of one empty space between two filled spaces (Bertulis & Bulatov, 2001; Bertulis, Surkys, Bulatov, & Gutauskas, 2009). One might have supposed that, in the present study, increasing the contrast of the surrounding filled spaces would have strengthened the illusion, and so decreased the perceived width of the aperture. However, our manipulations of contrast (designed to mimic those in another study of real apertures, not reported here) also changed the average luminance, so that the lower contrast surrounds had a higher average luminance than the high contrast surrounds. There is evidence that brighter components of Oppel-Kundt figures appear more expanded (Dworkin & Bross, 1998), which could explain why the apertures with higher luminance surrounds appear narrower in our study. Whatever the origin of the effect, it appears to have practical implications for RPD patients, who demonstrated underestimation of body-scaled aperture width for all surround types. Our data suggest that collisions by RPD patients will be reduced if the luminance of aperture surrounds is high, since they will be less likely to judge that they will fit through an inadequate aperture.

4.5. Other explanations for the results 4.7. Possible role of medication One can ask whether effects of PD other than changes in visuospatial processing could account for the present pattern of results. The essentially normal behaviour of the LPD group suggests that the result cannot be explained by a general loss of confidence associated with impaired motor function or a diagnosis of PD. Similarly, an explanation based on increased harm avoidance does not fit the results: although both LPD and RPD patients report higher levels

It is possible that dopaminergic medication could have influenced perceptual processing, and so judgements of body-toaperture width. At the time of experimental testing all patients bar one were receiving levodopa, agonist medication, or a combination of the two. While the relationship between dopaminergic medication and cognition is likely to be complex (for a review, see

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Cools, 2006), dopaminergic medication may interact with asymmetry to influence cognitive function in PD (Tomer, Aharon-Peretz, & Tsitrinbaum, 2007). Additionally, dopamine replacement therapy can impair proprioceptive processing (Mongeon et al., 2009; O’Suilleabhain, Bullard, & Dewey, 2001), which may be relevant to observed changes in body-centred frame of reference. However, the relationship found here between lateralised motor symptoms in an ‘OFF’ state and aperture task performance (in an ‘ON’ state) indicates that the observed deficits are most likely disease-related and not an unintended consequence of medication. 4.8. Possible gender effects The RPD group in the present study was predominantly male whereas the LPD and control groups had approximately equal numbers of males and females. In healthy populations, females are more accurate in judging the smallest aperture through which they can walk frontally (Lopresti-Goodman et al., 2009). Further, there are gender differences in PD in both self-reported visuospatial problems and in a range of visuospatial and perceptual tasks (Davidsdottir et al., 2005, 2008). In the present study, the relatively small number of females in each subgroup did not allow for a meaningful comparison of the performance of males and females. However, the impaired perception of RPD patients appeared not to be a gender effect, in that the slight discrepancy in gender ratios between patient subgroups (and controls) failed to account for the contrasting patterns of body-to-aperture width judgements. 4.9. Conclusions and future directions Visual and motor functions are highly integrated, and the relevance of abnormal perceptual processing to common problems of mobility in PD, such as veering, shuffling, collisions and FOG is receiving increasing attention (Davidsdottir et al., 2005, 2008; Lee et al., 2001a; Rahman et al., 2008). The present task required participants to imagine themselves on a railway track heading towards a doorway and to judge whether or not the widest part of their body (shoulders) would fit through the doorway without turning. Although this differs from actually walking through a gap, the judgement in both tasks must be made relative to the same standard, a body-centred judgement, or in Gibson’s phrase, the ‘affordance’ of the doorway (Gibson, 1979). The results indicate that, close to an aperture, where adjustments to heading and/or posture in normal locomotion are most likely to take place, RPD patients underestimate their body size relative to aperture size, and so appear particularly at risk of mobility problems in confined spaces. In previous questionnaire research, patients with right disease-onset reported bumping into both left and right sides of doorways (Davidsdottir et al., 2005), consistent with a perceptual misjudgement of body-to-aperture size rather than errors related to asymmetric gait or visuospatial asymmetry. It has also been postulated that perceptual errors in PD might have a causal role in freezing episodes in confined spaces (Lee et al., 2001a). In the present study, although RPD patients tended to report more severe disturbances to gait than LPD on the GFQ, their frequency and severity was not significantly related to the extent of (mis)judgements of body-to-aperture size. However, the GFQ predominantly focuses on FOG and festinating gait, and the perceptual changes found here in RPD may contribute more to other impairments of gait, such as veering and collisions. Research on navigation and gait in PD that includes relevant tests of perception, such as the one adopted in this study, are needed to clarify the nature of any such associations and the degree to which they are mediated by disease asymmetry. Recently, Davidsdottir et al. (2008) have shown that (opposite) shifts in the egocentric midline in both LPD and RPD and the extent of visual dependence in RPD are associated with the extent of lateral

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veering when walking down a virtual corridor. In the same study, patients with higher levels of visual dependence tended to report bumping into doorways more frequently. Such studies, perhaps focussing on the degree of right-to-left motor symptom asymmetry in PD, are needed to understand the role of perceptual abnormality in patients’ problems with navigation in everyday settings. Acknowledgements The work reported in this article was supported by grants from the Engineering and Physical Sciences Research Council (EPSRC) and from the Parkinson’s Disease Society of the UK. We thank the Parkinson’s Disease Society, Dr. Jeremy Stern, and Dr. A. Espley for their assistance in recruiting participants for this study, the participants themselves for their time and commitment, and the reviewers for helpful suggestions. References Abler, B., Hahlbrock, R., Unrath, A., Grön, G., & Kassubek, J. (2009). At-risk for pathological gambling: Imaging neural reward processing under chronic dopamine agonists. Brain, 132, 2396–2402. Adamovich, S. V., Berkinblit, M. B., Hening, W., Sage, J., & Poizner, H. (2001). The interaction of visual and proprioceptive inputs in pointing to actual and remembered targets in Parkinson’s disease. Neuroscience, 104, 1027–1041. Amick, M. M., Schendan, H. E., Ganis, G., & Cronin-Golomb, A. (2006). Frontostriatal circuits are necessary for visuomotor transformation: Mental rotation in Parkinson’s disease. Neuropsychologia, 44, 339–349. Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Manual for the Beck depression inventory (2nd ed.). San Antonio, TX: Psychological Corp. Benton, A. L., & Hamsher, K. (1976). Multilingual aphasia examination. Iowa City: University of Iowa. Bertulis, A., & Bulatov, A. (2001). Distortions of length perception in human vision. Biomedicine, 1, 3–23. Bertulis, A., Surkys, T., Bulatov, A., & Gutauskas, A. (2009). Three-part Oppel-Kundt illusory figure. Medicina (Kaunas, Lithuania), 45, 871–877. Bodis-Wollner, I., Marx, M. S., Mitra, S., Bobak, P., Mylin, L., & Yahr, M. (1967). Visual dysfunction in Parkinson’s disease. Loss of spatiotemporal contrast sensitivity. Brain, 110, 1675–1698. Booij, J., Tissingh, G., Boer, G. J., Speelman, J. D., Stoof, J. C., Janssen, A. G., et al. (1997). [123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 62, 133–140. Clower, D. M., Dum, R. P., & Strick, P. L. (2005). Basal ganglia and cerebellar inputs to‘AIP’. Cerebral Cortex, 15, 913–920. Cools, R. (2006). Dopaminergic modulation of cognitive function implications for LDOPA treatment in Parkinson’s disease. Neuroscience and Biobehavioral Reviews, 30, 1–23. Cooper, C. A., Mikos, A. E., Wood, M. F., Kirsch-Darrow, L., Jacobson, C. E., Okun, M. S., et al. (2008). Does laterality of motor impairment tell us something about cognition in Parkinson’s disease? Parkinsonism and Related Disorders, 15, 315–317. Costafreda, S. G., Fu, C. H., Lee, L., Everitt, B., Brammer, M. J., & David, A. S. (2006). A systematic review and quantitative appraisal of fMRI studies of verbal fluency: Role of the left inferior frontal gyrus. Human Brain Mapping, 27, 799–810. Cronin-Golomb, A. (2010). Parkinson’s disease as a disconnection syndrome. Neuropsychology Review, 20, 191–208. Crum, R. M., Anthony, J. C., Bassett, S. S., & Folstein, M. F. (1993). Population-based norms for the Mini-Mental State examination by age and educational level. Journal of American Medical Association, 269, 2386–2391. Davidsdottir, S., Cronin-Golomb, A., & Lee, A. (2005). Visual and spatial symptoms in Parkinson’s disease. Vision Research, 45, 1285–1296. Davidsdottir, S., Wagenaar, R., Young, D., & Cronin-Golomb, A. (2008). Impact of optic flow perception and egocentric coordinates on veering in Parkinson’s disease. Brain, 131, 2882–2893. Deijen, J. B., Stoffers, D., Berendse, H. W., Wolters, E., & Theeuwes, J. (2006). Abnormal susceptibility to distracters hinders perception in early stage Parkinson’s disease: A controlled study. BMC Neurology, 6, 43–52. Dworkin, L., & Bross, M. (1998). Brightness contrast and exposure time effects on the Oppel-Kundt illusion. Perception, 27(Suppl.), 87. Ehrsson, H. H., Kito, T., Sadato, N., Passingham, R. E., & Naito, E. (2005). Neural substrate of body size: Illusory feeling of shrinking of the waist. PLoS Biology, 3, e412. Fahn, S., Elton, R. L., & Members of the UPDRS Development Committee. (1987). United Parkinson’s disease rating scale. In S. Fahn, C. D. Marsden, D. B. Calne, & M. Goldstein (Eds.), Recent developments in Parkinson’s disease (pp. 153–164). Florham Park, NJ: Macmillan Health Care Information. Fink, G. R., Marshall, J. C., Shah, N. J., Weiss, P. H., Halligan, P. W., Grosse-Ruyken, M., et al. (2000). Line bisection judgements implicate right parietal cortex and cerebellum as assessed by fMRI. Neurology, 54, 1324–1331.

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